Our broad objective is to understand how various nutritional and hormonal factors govern the synthesis of fat in animals. We are particularly interested in the very rapid and large activation which we have observed almost immediately after mice ingest a fat-free, glucose- rich test meal. The flux of glucose C to fatty acids (micron gC/min) in mice before and shortly after they ingest various glucose-rich test meals will be estimated in steady and non-steady states. Steady states in fed mice will be obtained by suppressing alimentary hyperglycemia (feeding 2 consecutive test meals). (U-C14) glucose will either be injected intravenously or added to the test meals. Serial measurements in individual mice of plasma glucose concentrations and specific activities, and measurement of total lipid fatty acid -C14 in various tissues at one point in time are the data required for the flux estimates. Among the parameters to be studied are: (a) influence of non-carbohydrate nutrients, (b) rates of lipogenic activation and inactivation, (c) tissues in which lipogenic activation occurs, (d) magnitude of the changes, (e) effects of multiple meals and prior fasting, (f) re-evaluation of quantitative differences in lipogenic activation between nibblers and gorgers, (g) requirements for insulin (diabetic mice) and other hormones, and (h) relationship of lipogenic activation to carbohydrate-induced hypo- and hypertriglyceridemias. In later years, we shall investigate the molecular basis of rapid lipogenic activation.